Overexpression of SIRT1 Protects Pancreatic β-Cells Against Cytokine Toxicity by Suppressing the Nuclear Factor-κB Signaling Pathway

OBJECTIVE—SIRT1, a class III histone/protein deacetylase, is known to interfere with the nuclear factor-κB (NF-κB) signaling pathway and thereby has an anti-inflammatory function. Because of the central role of NF-κB in cytokine-mediated pancreatic β-cell damage, we postulated that SIRT1 might work in pancreatic β-cell damage models

Standardizing definitions and reporting guidelines for the infertility core outcome set : an international consensus development study

Acknowledgments We would like to thank the consensus development meeting participants and colleagues at the Cochrane Gynaecology and Fertility Group, University of Auckland, New Zealand. Funding This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data or manuscript preparation. Siladitya Bhattacharya was supported by the University of Auckland Foundation Seelye Travelling Fellowship. B.W.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548) This article has not been externally peer reviewed. This article has been published simultaneously in Fertility and SterilityPeer reviewedPublisher PD

External validation and calibration of IVFpredict:A national prospective cohort study of 130,960 in vitro fertilisation Cycles

© 2015 Smith et al. Background Accurately predicting the probability of a live birth after in vitro fertilisation (IVF) is important for patients, healthcare providers and policy makers. Two prediction models (Templeton and IVFpredict) have been previously developed from UK data and are widely used internationally. The more recent of these, IVFpredict, was shown to have greater predictive power in the development dataset. The aim of this study was external validation of the two models and comparison of their predictive ability. Methods and Findings 130,960 IVF cycles undertaken in the UK in 2008-2010 were used to validate and compare the Templeton and IVFpredict models. Discriminatory power was calculated using the area under the receiver-operator curve and calibration assessed using a calibration plot and Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of reliability and resolution, were calculated to assess overall accuracy. Both models were compared after updating for current live birth rates to ensure that the average observed and predicted live birth rates were equal. The discriminative power of both methods was comparable: the area under the receiver-operator curve was 0.628 (95% confidence interval (CI): 0.625-0.631) for IVFpredict and 0.616 (95% CI: 0.613-0.620) for the Templeton model. IVFpredict had markedly better calibration and higher diagnostic accuracy, with calibration plot intercept of 0.040 (95% CI: 0.017-0.063) and slope of 0.932 (95% CI: 0.839 - 1.025) compared with 0.080 (95% CI: 0.044-0.117) and 1.419 (95% CI: 1.149-1.690) for the Templeton model. Both models underestimated the live birth rate, but this was particularly marked in the Templeton model. Updating the models to reflect improvements in live birth rates since the models were developed enhanced their performance, but IVFpredict remained superior. Conclusion External validation in a large population cohort confirms IVFpredict has superior discrimination and calibration for informing patients, clinicians and healthcare policy makers of the probability of live birth following IVF

Nitric oxide synthases and tubal ectopic pregnancies induced by Chlamydia infection: basic and clinical insights

Human ectopic pregnancy (EP) remains a common cause of pregnancy-related first trimester death. Nitric oxide (NO) is synthesized from L-arginine by three NO synthases (NOS) in different tissues, including the Fallopian tube. Studies of knockout mouse models have improved our understanding of the function of NOS isoforms in reproduction, but their roles and specific mechanisms in infection-induced tubal dysfunction have not been fully elucidated. Here, we provide an overview of the expression, regulation and possible function of NOS isoforms in the Fallopian tube, highlighting the effects of infection-induced changes in the tubal cellular microenvironment (imbalance of NO production) on tubal dysfunction and the potential involvement of NOS isoforms in tubal EP after Chlamydia trachomatis genital infection. The non-equivalent regulation of tubal NOS isoforms during the menstrual cycle suggests that endogenous ovarian steroid hormones regulate NOS in an isoform-specific manner. The current literature suggests that infection with C. trachomatis induces an inflammatory response that eventually leads to tubal epithelial destruction and functional impairment, caused by a high NO output mediated by inducible NOS (iNOS). Therefore, tissue-specific therapeutic approaches to suppress iNOS expression may help to prevent ectopic implantation in patients with prior C. trachomatis infection of the Fallopian tube

Developing a core outcome set for future infertility research : An international consensus development study

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form

Developing a minimum data set, known as a core outcome set, for future infertility research

Background: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and outcome reporting bias, make the results of infertility research difficult to interpret. Objectives: To develop a core outcome set to standardise outcome selection, collection, and reporting across future randomized controlled trials and systematic reviews evaluating potential treatments for infertility. Methods: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods including a three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries) (1). Results: The core outcome set consists of: (1) viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancies); (2) pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); (3) live birth; (4) gestational age at delivery; (5) birth weight; (6) neonatal mortality; and (7) major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Conclusions: Embedding the core outcome set within randomized controlled trials and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including Cochrane Gynaecology and Fertility Group, Fertility and Sterility, and Human Reproduction, have committed to implementing this core outcome set

Developing a core outcome set for future infertility research: an international consensus development study.

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Ferility and Sterility, and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund, and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. Hans Evers reports being the Editor Emeritus of Human Reproduction. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Annika Strandell reports consultancy fees from Guerbet. Ernest Ng reports research sponsorship from Merck. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023

Migrant children within Europe: a systematic review of children’s perspectives on their health experiences

Objectives: To review the extant literature in order to explore what is known about children’s own perspectives on the ir health experiences , focusing upon children and young people who have migrated into, and within, Europe. Study Design: A systematic review with narrative synthesis. Methods: A review of English language articles was performed in June 2016 using the following databases: Medline, CINAHL, Coc hrane and Web of Science. Included papers had to report data generated directly with children, up to 18 years of age, who had migrated across national borders into, or within, Europe during their own lifetimes. Extraction from articles was undertaken by a ll authors and quality assessment of included reviews was performed using the Mixed Methods Appraisal Tool ( MMAT ) . Results: The articles in the final dataset included research based on 4 broad areas: alcohol, smoking and substance use; diet, eating disorde rs and overweight; emotional, psychological and mental health issues and; children’s views and experiences of health and health services. The majority of studies were cross - sectional analytic or incidence or prevalence studies. Conclusion: There is a gene ral lack of clarity in the literature regarding the reporting of children’s own migration status. Children’s voices are often subsumed within those of their adult parents or carers. There is a need to promote more child - focussed research which gives voice to migrant children to better understand the complex and multidimensional factors that contribute to their (ill) health

Developing a core outcome set for future infertility research: an international consensus development study

Study Question Can a core outcome set to standardize outcome selection, collection, and reporting across future infertility research be developed? Summary Answer A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCT) and systematic reviews evaluating potential treatments for infertility. What is Known Already Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. Study Design, Size, Duration A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). Participants/Materials, Setting, Methods Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. Main Results and the Role of Chance The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Limitations, Reasons for Caution We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition, and an arbitrary consensus threshold. Wider Implications of the Findings Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Ferility and Sterility, and Human Reproduction, have committed to implementing this core outcome set